1uzw

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[[Image:1uzw.gif|left|200px]]<br />
 
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<applet load="1uzw" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1uzw, resolution 1.30&Aring;" />
 
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'''ISOPENICILLIN N SYNTHASE WITH L-D-(A-AMINOADIPOYL)-L-CYSTEINYL-D-ISODEHYDROVALINE'''<br />
 
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==Overview==
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==ISOPENICILLIN N SYNTHASE WITH L-D-(A-AMINOADIPOYL)-L-CYSTEINYL-D-ISODEHYDROVALINE==
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Isopenicillin N synthase (IPNS) is a non-haem iron oxidase that catalyses, the formation of bicyclic isopenicillin N from, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). In this study we, report a novel activity for the iron of the IPNS active site, which, behaves as a Lewis acid to catalyse the elimination of HF from the, fluorinated substrate analogue, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-beta-fluorovaline (ACbetaFV)., X-Ray crystallographic studies of IPNS crystals grown anaerobically with, ACbetaFV reveal that the valinyl beta-fluorine is missing from the active, site region, and suggest the presence of the unsaturated tripeptide, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-isodehydrovaline in place of, substrate ACbetaFV. (19)F NMR studies confirm the release of fluoride from, ACbetaFV in the presence of the active IPNS enzyme. These results suggest, a new mode of reactivity for the IPNS iron centre, a mechanism of action, that has not previously been reported for any of the iron oxidase enzymes.
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<StructureSection load='1uzw' size='340' side='right'caption='[[1uzw]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1uzw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_nidulans Aspergillus nidulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UZW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UZW FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDH:D-(L-A-AMINOADIPOYL)-L-CYSTEINYL-D-ISODEHYDROVALINE'>CDH</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uzw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uzw OCA], [https://pdbe.org/1uzw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uzw RCSB], [https://www.ebi.ac.uk/pdbsum/1uzw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uzw ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/IPNA_EMENI IPNA_EMENI] Isopenicillin N synthase; part of the gene cluster that mediates the biosynthesis of penicillin, the world's most important antibiotic (PubMed:3319778, PubMed:11755401). IpnA catalyzes the cyclization of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) to form isopenicillin N (IPN) that contains the beta-lactam nucleus (PubMed:3319778, PubMed:11755401, PubMed:28703303). The penicillin biosynthesis occurs via 3 enzymatic steps, the first corresponding to the production of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) by the NRPS acvA. The tripeptide ACV is then cyclized to isopenicillin N (IPN) by the isopenicillin N synthase ipnA that forms the beta-lactam nucleus. Finally, the alpha-aminoadipyl side chain is exchanged for phenylacetic acid by the isopenicillin N acyltransferase penDE to yield penicillin in the peroxisomal matrix (By similarity).[UniProtKB:P08703]<ref>PMID:11755401</ref> <ref>PMID:28703303</ref> <ref>PMID:3319778</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uz/1uzw_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1uzw ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Isopenicillin N synthase (IPNS) is a non-haem iron oxidase that catalyses the formation of bicyclic isopenicillin N from delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). In this study we report a novel activity for the iron of the IPNS active site, which behaves as a Lewis acid to catalyse the elimination of HF from the fluorinated substrate analogue, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-beta-fluorovaline (ACbetaFV). X-Ray crystallographic studies of IPNS crystals grown anaerobically with ACbetaFV reveal that the valinyl beta-fluorine is missing from the active site region, and suggest the presence of the unsaturated tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-isodehydrovaline in place of substrate ACbetaFV. (19)F NMR studies confirm the release of fluoride from ACbetaFV in the presence of the active IPNS enzyme. These results suggest a new mode of reactivity for the IPNS iron centre, a mechanism of action that has not previously been reported for any of the iron oxidase enzymes.
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==About this Structure==
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Active-site-mediated elimination of hydrogen fluoride from a fluorinated substrate analogue by isopenicillin N synthase.,Grummitt AR, Rutledge PJ, Clifton IJ, Baldwin JE Biochem J. 2004 Sep 1;382(Pt 2):659-66. PMID:15175003<ref>PMID:15175003</ref>
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1UZW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Emericella_nidulans Emericella nidulans] with FE2, SO4 and CDH as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Isopenicillin-N_synthase Isopenicillin-N synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.21.3.1 1.21.3.1] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UZW OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Active-site-mediated elimination of hydrogen fluoride from a fluorinated substrate analogue by isopenicillin N synthase., Grummitt AR, Rutledge PJ, Clifton IJ, Baldwin JE, Biochem J. 2004 Sep 1;382(Pt 2):659-66. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15175003 15175003]
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</div>
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[[Category: Emericella nidulans]]
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<div class="pdbe-citations 1uzw" style="background-color:#fffaf0;"></div>
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[[Category: Isopenicillin-N synthase]]
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[[Category: Single protein]]
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[[Category: Baldwin, J.E.]]
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[[Category: Clifton, I.J.]]
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[[Category: Grummitt, A.R.]]
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[[Category: Rutledge, P.J.]]
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[[Category: CDH]]
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[[Category: FE2]]
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[[Category: SO4]]
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[[Category: antibiotic biosynthesis]]
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[[Category: b-lactam antibiotic]]
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[[Category: oxidoreductase]]
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[[Category: oxygenase]]
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[[Category: penicillin biosynthesis]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 17:17:22 2007''
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==See Also==
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*[[Isopenicillin N synthase|Isopenicillin N synthase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Aspergillus nidulans]]
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[[Category: Large Structures]]
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[[Category: Baldwin JE]]
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[[Category: Clifton IJ]]
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[[Category: Grummitt AR]]
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[[Category: Rutledge PJ]]

Current revision

ISOPENICILLIN N SYNTHASE WITH L-D-(A-AMINOADIPOYL)-L-CYSTEINYL-D-ISODEHYDROVALINE

PDB ID 1uzw

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